Trimethylsilyl iodide → N-(((R)-1-(4-aminobutanoyl)pyrrolidin-2-yl)methyl)-6-(2-cyanophenyl)-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamide

HRID 2080305Notes

Reaction equation

HRID 2080305 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:39]=[CH:38][C:12]([C:13]([NH:15][CH2:16][C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2[C:22](=[O:37])[CH2:23][CH2:24][CH2:25][NH:26]C(=O)OCC2C=CC=CC=2)=[O:14])=[C:11]([NH:40][CH2:41][CH2:42][CH:43]2[CH2:48][CH2:47][CH2:46][CH2:45][O:44]2)[N:10]=1)#[N:2].[Si](I)(C)(C)C>CC#N>[NH2:26][CH2:25][CH2:24][CH2:23][C:22]([N:18]1[CH2:19][CH2:20][CH2:21][C@@H:17]1[CH2:16][NH:15][C:13](=[O:14])[C:12]1[CH:38]=[CH:39][C:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:1]#[N:2])=[N:10][C:11]=1[NH:40][CH2:41][CH2:42][CH:43]1[CH2:48][CH2:47][CH2:46][CH2:45][O:44]1)=[O:37]

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 57542296benzyl 4-((R)-2-((6-(2-cyanophenyl)-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamate

Product 1

HCID 57542872N-(((R)-1-(4-aminobutanoyl)pyrrolidin-2-yl)methyl)-6-(2-cyanophenyl)-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamideYield 96.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of benzyl 4-((R)-2-((6-(2-cyanophenyl)-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamate (47 mg, 0.072 mmol) in MeCN (1 mL) at 0° C. was added TMSI (72 mg, 0.36 mmol). The mixture was stirred at room temperature for 2 hrs and purified on RP-HPLC using a mixture of acetonitrile and H2O to give N—(((R)-1-(4-aminobutanoyl)pyrrolidin-2-yl)methyl)-6-(2-cyanophenyl)-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamide (36 mg, 77%). LRMS (M+H+) m/z 519.3.

Workup

  1. custompurified on RP-HPLC
  2. additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record
ord-a0ebe1874ab04ee290fa30175ea04c72
Source dataset
uspto-grants-2011_04
Patent number
US07932270B2

Reaction notes

Loading…